Most cells, tissues, and organs of the human body require oxygen to carry out their normal physiologic functions and to maintain viability. This oxygen is obtained from the atmosphere by the lungs, carried predominantly by hemoglobin molecules in the blood, and delivered to the cells, tissues, and organs of the body by the circulatory system. If the lungs can not provide sufficient oxygen to the blood, if there is insufficient hemoglobin in the blood (i.e., anemia) to carry sufficient oxygen, if the heart cannot pump an adequate volume of blood over time to the various organs of the body, or if there is blockage of blood flow to one or more regions of the circulation, the affected cells will suffer from lack of adequate oxygen, a condition known as tissue hypoxia.
An important goal in the clinical management of critically ill patients is ensuring the adequacy of tissue oxygenation. A variety of means are in use to help achieve this goal. Among these, pulmonary artery catheterization is commonly used to allow determination of cardiac output, mixed venous oxygen saturation and partial pressure, and derivation of oxygenation transport variables such as systemic oxygen delivery, systemic oxygen consumption, and systemic oxygen extraction. However, these conventional hemodynamic and oxygen-derived parameters can be insensitive to mild, moderate, early, or compensated stages of perfusion failure, and to regional tissue hypoperfusion, including ischemia, or hypoxia involving areas such as the gastro-intestinal tract.
If tissue hypoxia is sufficiently severe, the hypoxic cells produce lactic acid. This allows the cells to produce needed energy in the absence of oxygen, and provides a temporary means of maintaining cellular function and viability. It is temporary because this excessive acid production results in a decrease of the pH within and around the cells, and this decrease in pH will itself eventually threaten the functional capacity and viability of the affected cells. Thus, detecting a decrease in the pH inside cells comprising a tissue or organ can serve as an indicator of tissue hypoxia.
Measurement of the pH of the cells lining the stomach (gastric intramucosal pH), intestines, or other organs or tissues of the body can be performed using a technique known as hollow viscus tonometry, in which a walled chamber is placed within a hollow organ such as the stomach. The walled chamber, which may be in the form of a balloon, is constructed of material that is permeable to carbon dioxide (CO.sub.2) gas, but effectively impermeable to liquid. When filled with a liquid such as water or saline solution and situated within the hollow viscus, such a balloon will allow the passage of CO.sub.2 gas from the hollow viscus to pass through the membrane of the balloon and become dissolved in the liquid solution contained within the balloon. In time, the level of CO.sub.2 in solution within the balloon will equal or be proportional to the level of CO.sub.2 within the hollow viscus. Because biological membranes, including the membranes that compose the surface of the cells lining the stomach and other hollow organs, are also permeable to CO.sub.2 gas, the level of CO.sub.2 within the hollow viscus will, under certain undisturbed circumstances, be equal to or approximately equal to the level of CO.sub.2 within the cells comprising or lining the viscus.
Thus, if the liquid-filled balloon is allowed to sit within a hollow viscus such as the stomach or intestine for a sufficient period of time, and then the liquid is aspirated from the balloon by a catheter connected to the balloon and analyzed in a laboratory to determine the level of CO.sub.2 gas dissolved within the liquid, the level of CO.sub.2 gas inside the cells lining the viscus (intramucosal pCO.sub.2) can be ascertained. If intramucosal pCO.sub.2 is known, then intramucosal pH can be determined using a mathematical formula that relates pH to pCO.sub.2. This formula also requires that a third variable is known, namely the concentration of bicarbonate ions inside the cells comprising or lining the viscus. This intracellular bicarbonate concentration is equal to or approximately equal to the concentration of bicarbonate ions in arterial blood, serum, or plasma, and the latter can be readily determined by a blood test.
As is common clinical practice, this blood test is frequently performed in most hospitalized, critically ill patients treated in an intensive care unit setting, often being performed daily or even several times each day. The bicarbonate concentration can be obtained by direct measurement, or calculated from the results of other blood tests using a mathematical equation (see Kruse J. A., Hukku P., Carlson R. W.: "Relationship Between The Apparent Dissociation Constant Of Blood Carbonic Acid And Severity Of Illness," 114 J. Lab. Clin. Med. 568-574 (1989)).
According to information from scientific studies that have been reported in the published biomedical literature, tonometry is a useful means of evaluating splanchnic intramucosal pCO.sub.2 and pH, referring to the cells lining or comprising certain portions of the gastrointestinal tract and certain adjacent organs or tissues, thereby indirectly evaluating the adequacy of splanchnic blood flow and oxygenation. In trauma, shock, and sepsis, the body selectively diverts splanchnic blood flow to the heart, lungs, and brain, thus making the gastrointestinal tract a sensitive and early diagnostic indicator of systemic ischemia, hypoperfusion, and hypoxia. Furthermore, the available information indicates that determination of tissue pH is a valuable prognostic indicator of survival among critically ill patients hospitalized in the intensive care unit setting, and that it is a better prognostic indicator than any of the conventional hemodynamic and oxygen-derived physiological variables.
U.S. Pat. No. 4,643,192 is illustrative of tonometric methods, and is incorporated herein by reference. An illustrative device is described in Catalog No. 2002-48-16, TRIP.RTM. NGS CATHETER, Datex-Engstrom, Inc., Tewksbury, Mass., which is also incorporated herein by reference.
A major drawback of the previously described method of performing hollow viscus tonometry, using the device and technique briefly described above, is that it requires a specified period of time to arrive at the measurement result. Under ideal circumstances this time period is typically about one hour, but can be substantially longer. This obligatory time period is necessary because the events listed below must take place after the catheter has been placed within the body. All are required in order to arrive at a single value of tissue pH and/or tissue pCO.sub.2. In the following, it is assumed that the organ in which the tonometry catheter has been placed is the stomach, although the same requirements are expected for placement in other parts of the body:
1. A measured volume of liquid must be carefully introduced through the tonometry catheter and into the balloon.
2. CO.sub.2 gas dissolved in the liquid residing within the tonometry balloon must reach or approach equilibrium with the CO.sub.2 gas within the hollow of the stomach.
3. Liquid must be carefully aspirated from the tonometry balloon by the tonometry catheter. For accurate measurements, it may be necessary to ensure that the liquid within the dead space volume of the catheter tube is aspirated and discarded, prior to aspirating and collecting liquid that had resided within the balloon.
4. The aspirated liquid must be sealed within a gas-tight container. Prior to sealing, any air bubbles must be expelled from the container lest they alter the level of CO.sub.2 dissolved in the liquid.
5. The liquid specimen must be transported to a laboratory or location where assay instruments are available to measure the level or partial pressure of CO.sub.2 gas within the liquid specimen.
6. The aspirated liquid must be assayed for the level or partial pressure of CO.sub.2 gas within the liquid specimen. A skilled laboratory technician is required to perform the laboratory analysis that measures the level of CO.sub.2 dissolved in the liquid specimen.
7. If insufficient time was allowed for complete equilibration while the liquid was within the balloon (typically less than about 90 minutes), the result of the CO.sub.2 assay must be mathematically adjusted to obtain an estimate of the steady-state, equilibrium value. Even if the elapsed time was sufficient for complete equilibration, a mathematical adjustment is still required to account for the expected gradient between the level or partial pressure of CO.sub.2 external to the balloon and the level or partial pressure of CO.sub.2 dissolved in the liquid within the balloon.
8. Tissue pH must be mathematically derived from the adjusted value of the level or partial pressure of CO.sub.2 dissolved in the liquid using the Henderson-Hasselbalch equation or a modification thereof.
The obligatory time for completing the above steps limits the frequency of the measurements, and in some cases makes repeated measurements within a certain time frame impossible or impractical. In addition, each of the steps must be carried out by personnel specifically trained and skilled in the above techniques, and the techniques are cumbersome to perform.
The elapsed time between filling the tonometry balloon with liquid and aspirating the liquid must be accurately determined so that the steady-state value of CO.sub.2 within the balloon liquid can be accurately estimated from the measured value of CO.sub.2 within the balloon liquid. Certain CO.sub.2 analyzers that are commonly used in clinical laboratories have been shown to yield erroneous CO.sub.2 assay results when used to measure pCO.sub.2 in aspirated liquid specimens obtained from standard tonometry catheters. (See, e.g., Riddington et al., "Potential Hazards In Estimation Of Gastric Intramucosal pH", 340 Lancet 547 (1992); Takala et al., "Saline PCO.sub.2 Is An Important Source Of Error In The Assessment Of Gastric Intramucosal pH", 22 Crit. Care Med. 1877-79 (1994)). Still further, the mathematics involved entail another level of understanding and training necessary to correctly obtain the final measurement value of tissue pH. This calculation generally requires the use of a calculating aid such as an electronic calculator or computer.
Besides the cumbersome sequence of techniques and the obligatory time needed to arrive at measurements of tissue pH, determination of tissue pH by this means at best provides only intermittent measurements, each isolated to a single point in time usually separated by a matter of hours. The existing art does not allow for a means of providing continuous measurements of tissue pCO.sub.2 or tissue pH.